Biomedical subjects

Alan Phillips

Publications and source records attributed to Alan Phillips.

7 recordsLinked to original sources

PubMed2006

Making sense of syphilis: beliefs, behaviours and disclosure among gay men recently diagnosed with infectious syphilis and the implications for prevention.

BACKGROUND: The resurgence of syphilis in men who have sex with men (MSM) has proved remarkably resilient in the face of innovative control and prevention interventions. Understanding the determinants of the current outbreaks has been restricted by the available data. Qualitative work is needed to understand individual and community experiences of syphilis and to help guide new prevention and control efforts. METHODS: An exploratory study using semi-structured interviews with a convenience sample of MSM (n = 15), recently diagnosed with infectious syphilis, attending sexual health and HIV-outpatient services in Brighton, England. RESULTS: Analysis focussed on men's beliefs about syphilis, their experience of testing and being given a syphilis diagnosis, mediators of 'risky' sexual behaviour and disclosure to social and sexual contacts. Two beliefs--'syphilis is rare' and 'syphilis is dirty'--dominated respondents' accounts. These beliefs coloured every aspect of respondents' clinical and social experience of syphilis, and impeded disclosure and partner notification. They also contributed to misconceptions about behaviours with increased syphilis transmission risk, the mechanics of disease acquisition, health-seeking behaviours and risk-reduction strategies. CONCLUSIONS: The apparent failure of syphilis control measures so far may be due to our limited understanding of MSM's views and experience of STIs other than HIV Syphilis prevention needs to tackle MSM's widely held beliefs about sexual communication, risk behaviour and other STIs. The most useful health education interventions are likely to be those that build on MSM's significant knowledge base and address both the current syphilis crisis and wider sexual health promotion goals.

Adult↗

PubMed2005

EspJ is a prophage-carried type III effector protein of attaching and effacing pathogens that modulates infection dynamics.

Enterohemorrhagic Escherichia coli, enteropathogenic E. coli, and Citrobacter rodentium are highly adapted enteropathogens that successfully colonize their host's gastrointestinal tract via the formation of attaching and effacing (A/E) lesions. These pathogens utilize a type III secretion system (TTSS) apparatus, encoded by the locus of enterocyte effacement, to translocate bacterial effector proteins into epithelial cells. Here, we report the identification of EspJ (E. coli-secreted protein J), a translocated TTSS effector that is carried on the 5' end of the cryptic prophage CP-933U. Infection of epithelial cells in culture revealed that EspJ is not required for A/E lesion activity in vivo and ex vivo. However, in vivo studies performed with mice demonstrated that EspJ possesses properties that influence the dynamics of clearance of the pathogen from the host's intestinal tract, suggesting a role in host survival and pathogen transmission.

Animals↗

PubMed2005

Distribution of tccP in clinical enterohemorrhagic and enteropathogenic Escherichia coli isolates.

Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are diarrheagenic pathogens that colonize the gut through the formation of attaching and effacing lesions, which depend on the translocation of effector proteins via a locus of enterocyte effacement-encoded type III secretion system. Recently, two effector proteins, EspJ and TccP, which are encoded by adjacent genes on prophage CP-933U in EHEC O157:H7, have been identified. TccP consists of a unique N-terminus region and several proline-rich domains. In this project we determined the distribution of tccP in O157:H7, in non-O157 EHEC, and in typical and atypical EPEC isolates. All the EHEC O157:H7 strains tested were tccP(+). Unexpectedly, tccP was also found in non-O157 EHEC, and in typical and atypical EPEC isolates, particularly in strains belonging to serogroups O26 (EHEC), O119 (typical EPEC), and O55 (atypical EPEC). We recorded some variation in the length of tccP, which reflects diversity in the number of the proline-rich repeats. These results show the existence of a class of "attaching and effacing" pathogens which express a combination of EPEC and EHEC virulence determinants.

Animals↗

PubMed2003

ICH E9 guideline 'Statistical principles for clinical trials': a case study.

The International Conference on Harmonization (ICH) E9 guideline 'Statistical principles for clinical trials' was adopted by the Committee for Proprietary Medicinal Products in March 1998, and consequently is operational in Europe. It has also been adopted in the U.S.A. and Japan. The aim of this paper is to relate the problems encountered during a recent regulatory submission to those discussed in the ICH E9 guideline. Statistical principles discussed in the guideline, but not comprehensively addressed when the clinical development programme was initiated in the mid-1990s, will be reviewed. The impact of each issue on the approvability of the dossier will be discussed, together with recommendations on how to avoid such problems with other ongoing clinical development programmes.

Data Interpretation, Statistical↗

PubMed2002

A novel dispersin protein in enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is a diarrheal pathogen defined by its characteristic aggregative adherence (AA) to HEp-2 cells in culture. We have previously shown that EAEC strains secrete a 10-kDa protein that is immunogenic in a human EAEC challenge model. We report here that this protein is encoded by a gene (called aap) lying immediately upstream of that encoding the AggR transcriptional activator, and that aap is under AggR control. The product of aap has a typical signal sequence and is secreted to the extracellular milieu, where it remains noncovalently attached to the surface of the bacterium. EAEC aap mutants aggregate more intensely than the wild-type parent in a number of assays, forming larger aggregates and fewer individual bacteria. Infection of colonic biopsies with wild-type EAEC strain 042 and its aap mutant revealed more dramatic autoagglutination of the mutant compared with the wild-type parent. Our data suggest that the aap gene product participates in formation of a surface coat that acts to disperse the bacteria, thus partially counteracting aggregation mediated by aggregative adherence fimbriae. We have therefore named the aap gene product "dispersin," and we propose that it may be representative of a functional class of colonization factors. Since dispersin is expressed in vivo, is highly immunogenic, and is present in most EAEC strains, it holds considerable promise as an EAEC immunogen.

Agglutination↗

PubMedDate not supplied

Escherichia coli enterovirulent phenotypes in Zambians with AIDS-related diarrhoea.

Persistent diarrhoea is a major cause of morbidity and mortality in AIDS patients, and consequently an important public health problem in sub-Saharan Africa. Although intestinal protozoa and bacteria are detected in many of these patients, a substantial proportion of disease remains unexplained even after intensive investigation. HEp-2 cell adherent Escherichia coli have been described in AIDS patients with persistent diarrhoea, but their contribution to the overall burden of disease is not yet defined. We studied HEp-2 cell adherence of E. coli isolates from 116 adult Zambian AIDS patients and 153 healthy controls obtained in 1993 or 1998-99. Enteroaggregative, enteropathogenic, and diffusely adherent phenotypes were observed in E. coli isolates from both AIDS patients and controls, but cytotoxic phenotypes were only isolated from the AIDS patients. There was no evidence of seasonality in the frequency of isolation, and there was no evidence of long-term carriage. Light and electron microscopy of distal duodenal biopsies did not reveal any bacteria closely associated with the brush border. Isolates were less susceptible to amoxycillin, tetracycline, and sulfonamides than to newer antibiotics. Enterovirulent E. coli appear to contribute to intestinal disease in AIDS patients in Zambia but asymptomatic carriage is common. Antibiotic trials should be carried out.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Two new species of Botryosphaeria with brown, 1-septate ascospores and Dothiorella anamorphs.

Botryosphaeria sarmentorum sp. nov. and B. iberica sp. nov. are described and illustrated. These two species are unusual in this genus because of their brown, 1-septate ascospores. Phylogenetic analysis based on ITS and EF1-alpha sequences place them within the clade containing species with Fusicoccum anamorphs. The brown, 1-septate conidia, however, do not conform to Fusicoccum. Therefore phylogenetically and morphologically the anamorphs of these two species belong in a genus distinct from any of the currently accepted anamorph genera assigned to Botryosphaeria. Through a study of the type species of Dothiorella this genus is resurrected to accommodate anamorphs of Botryosphaeria with brown, 1-septate conidia. Botryosphaeria sarmentorum is shown to be the teleomorph of Diplodia sarmentorum, which in turn is transferred to Dothiorella. Otthia quercus is transferred to Botryosphaeria as B. quercicola nom. nov.

Ascomycota↗